Sustained release beads and suspensions including the same for sustained delivery of active ingredients

ABSTRACT

Sustained-released beads providing active ingredients over an extended period of time to an individual orally ingesting the sustained release beads. The sustained-release beads can be part of a suspension wherein the sustained-release beads are suspended and evenly dispersed in the suspension. Binding agents are used to form the structural framework of the sustained released beads and retain the active ingredients without chemical or electrical bonding. The components of the dispersion medium are GRAS designated, making the suspension suitable for use as a food product.

BACKGROUND

Individuals taking supplements and/or medications are often required toingest capsules or pills multiple times per week, and in some instances,multiple times per day, in order to receive the necessary amount of theactive ingredients contained therein at the appropriate time.Traditionally, this has required an individual to self-monitor theircapsule or pill in-take, such as through the use of a medication log ora pill box having multiple labeled compartments. These methods includeample opportunity for human error. Furthermore, the requirement ofhaving to take multiple pills per day or per week is cumbersome andinconvenient.

As an alternative, some medications and/or supplements have beenprovided in sustained-released pills. Sustained-released pills attemptto alleviate the burdens of taking numerous pills per day by providingrelatively large amounts of medicine in a single pill that graduallyreleases the quantity of medicine over an extended period of time onceingested. Generally speaking, pills of this type are limited to thedelivery of medicines regulated by the U.S. Food and DrugAdministration. Furthermore, the periods of time over which themedication is gradually released are relatively short, and almost alwaysless than 24 hours. Accordingly, these pills do not resolve the issuewhere an individual is required to take multiple doses of a medicationover several days, weeks or months.

Additionally, the options for sustained release of medication arebelieved to be mostly limited to pills or capsules. However, someindividuals finds pills or the like difficult to deal with. Forinstances, pills are generally small and can easily be lost if dropped.Also, many individuals have difficulty swallowing pills, especiallyyounger children.

One example of a sustained-release medicine in a non-capsule form is thecomposition described in U.S. Pat. No. 6,001,392. The compositiongenerally includes drug/resin complexes that may be carried in a liquidcomposition, wherein the drug is an antitussive. The drug/resincomplexes utilize cross-linked ion exchange resins, with the drugadsorbed on to the cross-linked ion exchange resin via ionic bondsbetween the drug and the ion-exchange resin. The manner of makingdrug/resin complexes using ion-exchange resins can be relativelycomplicated and expensive. Often, the ability to alter the period oftime over which the medication is released is controlled by usingsubstantial coating layers, rather than manipulating the drug/resincomplex. For example, some drug/resin complexes of the '392 patentrequire coating layers that are 50% w/w drug in order to providesustained release of the antitussive. The requirement for thisrelatively large amount of coating layer raises the overall price ofmanufacturing the drug/resin complexes.

The drug/resin complexes of the '392 patent may be carried by liquidcompositions that generally include ingredients that are not deemedsuitable for use in foods (either in any quantity of above certainquantities), such as polyethylene glycols (PEGs) and certainion-exchange resins. For example, the '392 patent utilizes AmberliteIR-69 as the ion exchange resin, which does not carry a GRAS (GenerallyRegarded As Safe) designation from the U.S. Food and DrugAdministration. Thus, while the '392 patent describes drinkable liquidcompositions for sustained release of antitussives, the '392 patent islimited to medicinal applications that are regulated by the U.S. Foodand Drug Administration.

SUMMARY

Disclosed are various embodiments of sustained-release beads includingbinding agents and active ingredients for oral ingestion by a mammal(e.g. a human) to thereby provide active ingredients to the mammal in asustained-released fashion. The sustained-release beads may be includedin a suspension wherein the sustained-release beads are evenly dispersedthroughout the suspension. In one particular feature of thesustained-release beads, the binding agents are cellulose-based and thesustained-release beads do not have an external coating. In anotherembodiment, the sustained-release beads include only ingredients thatare GRAS-compliant or present in GRAS-compliant quantities.

In one embodiment, a suspension includes a dispersion medium and adispersed phase. The dispersion medium includes an aqueous solution andone or more thickening agents. The dispersed phase includes one or moresustained-release beads. The sustained-release beads include one or morebinding agents and one or more active ingredients.

In another embodiment, a sustained-release bead includes one or morebinding agents and one or more active ingredients. The one or morebinding agents may be provided at from 40 wt % to 95 wt % of thesustained-release bead. The one or more active ingredients may beprovided at from 5 wt % to 60 wt % the sustained-release bead.

In still another embodiment, a method of making sustained-release beadsincludes forming a blend by blending together one or more binding agentsand one or more active ingredients. The method also includes forming awet mass by adding an aqueous to the blend. Further, the method includesforming extrudate by extruding the wet mass. Additionally, the methodincludes forming sustained-release beads by unitizing the extrudate.

In another embodiment, a beverage includes a receptacle and a suspensioncontained within the receptacle. The suspension includes a dispersionmedium and a dispersed phase. The dispersion medium includes an aqueoussolution and one or more thickening agents. The dispersed phase includesone or more sustained-release beads. Each sustained-release beadincludes one or more binding agents and one or more active ingredients.The beverage may be in the form of a sports drink that includes a fluidreceptacle and a fluid suspension contained in the fluid receptacle. Thefluid receptacle includes a base, a surrounding sidewall extendingupwardly from the base to terminate in an open mouth, and a closureadapted to releasably cover the mouth. The suspension includes adispersion medium and a dispersed phase. The dispersion medium includesan aqueous solution and one or more thickening agents. The dispersedphase includes one or more sustained-release beads. Eachsustained-release bead includes one or more binding agents and one ormore active ingredients.

In another embodiment, packetized sustained-release beads include apacket and a selected quantity of sustained-release beads contained inthe packet. Each of the sustained-release beads includes one or morebinding agents and one or more active ingredients. The one or morebinding agents may be provided at from 40 wt % to 95 wt % of thesustained-release bead. The one or more active ingredients may beprovided at from 5 wt % to 60 wt % of the sustained-release bead.

In another embodiment, a method for producing an orally ingestible fluidincludes providing one or more sustained-release beads, providing adispersion medium, and mixing the one or more sustained-release beads inthe dispersion medium. The sustained-release beads include one or morebinding agents and one or more active ingredients. The one or morebinding agents may be provided from 40 wt % to 95 wt % of thesustained-release bead. The one or more active ingredients may providefrom 5 wt % to 60 wt % the sustained-release bead. The dispersion mediumincludes an aqueous or organic solution and one or more thickeningagents.

It is to be understood that the foregoing is a brief summary of variousaspects of some disclosed embodiments. The scope of the disclosure neednot therefore include all such aspects or address or solve all issuesnoted in the background above. In addition, there are other aspects ofthe disclosed embodiments that will become apparent as the specificationproceeds.

The foregoing and other features, utilities, and advantages of thesubject matter described herein will be apparent from the following moreparticular description of certain embodiments as illustrated in theaccompanying drawings. In this regard, it is to be understood that thescope of the invention is to be determined by the claims as issued andnot by whether given subject includes any or all features or aspectsnoted in this Summary or addresses any issues noted in the Background.

BRIEF DESCRIPTION OF THE DRAWINGS

The preferred and other embodiments are disclosed in association withthe accompanying drawings in which:

FIG. 1 is a flow chart depicting a method for making sustained-releasebeads as disclosed herein;

FIG. 2 is a flow chart depicting a method for making an orallyingestible fluid as disclosed herein; and

FIG. 3 is a perspective view of a sports drink as disclosed herein.

DETAILED DESCRIPTION

In a first embodiment, active ingredients may be provided to a mammal,such as a human, in a sustained-released manner through the use of asuspension that is orally ingested by the mammal. The suspensiongenerally includes a dispersion medium and a dispersed phase, whereinthe dispersed phase includes a plurality of sustained-release beadssuspended in the dispersion medium. The sustained-release beads mayinclude one or more active ingredients and are configured in such a wayas to release the active ingredients over a period time rather than allat once. The dispersion medium is generally a fluid, such as a liquid ora gel, while the sustained-release beads of the dispersed phase aregenerally solid. Because of the nature of the suspension, thesustained-release beads remain suspended in the fluid dispersion mediumand do not dissolve in the dispersion medium.

The dispersion medium includes an aqueous solution. Any suitable aqueoussolution may be used, such as water, milk, fruit juice, alcohol, or thelike. Organic solutions may also be used for the dispersion medium. Theaqueous solution is preferably non-toxic or used in a non-toxic amount.In one embodiment, the aqueous solution may account for from 75 wt % toabout 99.5 wt % of the dispersion medium.

The dispersion medium also includes one or more thickening agents. Anysuitable thickening agent may be used for the dispersion medium. In oneembodiment, the thickening agent is non-toxic or used in a non-toxicquantity so that the suspension is safely ingestible. Suitablethickening agents include, but are not limited to, agar agar, xanthangum, guar gum, gelatin, acacia gum, pectin, ester gum, Arabic gum, andgullan gum. The amount of the one or more thickening agents in thedispersion medium is not limited and may be adjusted to arrive at anydesired viscosity for the dispersion medium. In one embodiment, thetotal amount of the one or more thickening agents in the dispersionmedium ranges from 0.05 wt % to 2 wt % of the dispersion medium. Inanother embodiment, a quantity of one or more thickening agents is addedto the aqueous solution until the dispersion medium has a viscosity inthe range of from about 0.894 cP to about 250,000 cP.

As noted above, one aim of including the one or more thickening agentsin the dispersion medium is to increase the viscosity of the dispersionmedium. By increasing the viscosity of the dispersion medium through theaddition of thickening agents, the dispersed phase of the suspensionwill be suspended throughout the dispersion medium, even after periodsof time during which settling might occur. When the beads of thedispersed phase are evenly suspended throughout the dispersion medium, agenerally consistent number of beads will be provided with each portionof the suspension ingested.

Additional components may also be included in the dispersion medium,such as components to further alter the consistency, appearance, taste,smell, or shelf life of the dispersion medium. In one embodiment, simplesyrup is included in the dispersion medium. Any amount of simple syrupmay be added. In one embodiment, simple syrup is added to the dispersionmedium at a rate of 1 part simple syrup for every 5 parts aqueoussolution. Sweetener may also be added to the dispersion medium. The typeof sweetener added to the dispersion medium is not limited and mayinclude natural and synthetic sweeteners. In one embodiment, thesweetener added to the dispersion medium is sugar, such as fructose,sucrose or ribose. In another embodiment, sweetener is excluded or adiet sweetener is used in order to make a diet dispersion medium. Whensweetener is used, it may be added in any suitable amount to alter thetaste of dispersion medium. Any suitable type and amount ofpreservatives may also be added to the dispersion medium. Additionally,any suitable type and amount of fragrance may be added to the dispersionmedium. Furthermore, any suitable type and amount of coloring may beadded to the dispersion medium.

In another embodiment, the dispersion medium is GRAS-compliant. GRASstatus is an American Food and Drug Administration (FDA) designationthat a chemical or substance added to food is considered safe byexperts, and so is exempted from the usual Federal Food, Drug, andCosmetic Act (FFDCA) food additive tolerance requirements. Most GRASsubstances have no quantitative restrictions as to use, but some GRASsubstances do have a quantitative limit for use in food. AGRAS-compliant dispersion medium may include a dispersion medium havingonly ingredients with a GRAS designation. For example, the dispersionmedium may contain a limited amount of polyethylene glycols (PEGs)because PEGs are GRAS substances that have a quantitative limit for usein food.

The dispersed phase of the suspension generally includes one or moresustained-release beads. As noted above, the sustained-release beads aregenerally solid and do not dissolve in the dispersion medium. When thedispersion medium has a suitable viscosity, the sustained-release beadsare suspended in the dispersion medium. In one embodiment, thesustained-release beads are uniformly dispersed throughout thedispersion medium. In another embodiment, the sustained-release beadscan be settled at the bottom of a dispersion medium and then dispersedby shaking the dispersion medium.

The sustained-release beads include one or more binding agents and oneor more active ingredients. The binding agents and active ingredientsare generally processed in such a way that both components are evenlydistributed throughout the sustained-release bead. The binding agentsserve to retain the shape of the sustained-release beads whilemaintaining the active ingredients in the sustained-release beads.Preferably, there are no chemical or electrical (e.g., ion sharing)reactions between the binding agents and the active ingredients. Rather,the sustained-release beads are held together and the active ingredientsare retained within the sustained-release beads by the structuralframework provided by the binding agents during processing of the beads.

Any suitable amount of each binding agent may be used in thesustained-release beads. In one embodiment, the total amount of bindingagents in the sustained-release beads may range from 40 wt % to 95 wt %of the sustained-release beads. In another embodiment, the total amountof binding agents in the sustained-release beads is approximately 50 wt% of the sustained-release beads. The amount of binding agent includedin each sustained-release bead may be adjusted in order to alter thesustained-release of the active ingredient once the suspension isingested. Generally speaking, a higher binding agent concentration inthe sustained-release beads will result in a slower sustained-release ofthe active ingredient. The dispersed phase may include beads havingdifferent binding agent concentrations such that the sustained-releasebeads release the active ingredients at varying time intervals,providing for sustained release of active ingredients over an extendperiod of time.

Any number of different binding agents may be used in thesustained-release beads. In one embodiment, the binding agents arenon-toxic or are used in non-toxic amounts. Exemplary binding agentsinclude, but are not limited to, methyl cellulose, ethyl cellulose,microcrystalline cellulose, croscarmellose sodium, dicalcium phosphate,cellulose, hypromellose, hydroxypropyl methylcellulose,carboxymethylcellulose, and hydroxyethyl cellulose. In one embodiment,only cellulose-based binding agents are used.

The amount of each active ingredient in the sustained-release beads isnot limited. In one embodiment, the total amount of active ingredientsin the sustained-release beads may range from 5 wt % to 60 wt % of thesustained-release beads. In another embodiment, the total amount ofactive ingredients in the sustained-release beads is approximately 50 wt% of the sustained-release beads. The concentration of activeingredients, the number of active ingredients and the type of activeingredients may vary amongst the various sustained-release beads used inthe suspension.

Any number of different active ingredients may be used in thesustained-release beads. Active ingredients may generally include anytype of element, compound, or combination or derivative therefore thatmay be administered to a mammal to effect a beneficial change in themammal's physical or mental state. In one embodiment, the class ofactive ingredients are those elements or compounds for aiding a mammalduring exercise. Exemplary active ingredients of this class includeelectrolytes, such as potassium, magnesium, sodium, and calcium, andstimulants, such as caffeine. Active ingredients may also includevitamins and minerals. Other exemplary active ingredients includeproteins, amino acids, hormones and organic acids. Other classes ofactive ingredients include, but are not limited to, those to fightdisease, those to prevent disease, those to alleviate or relieve pain,those to improve bone and joint health, those to improve mentalconcentration and alertness, those to improve physical appearance, andthose to combat mental illness. In one embodiment, the activeingredients are materials having a GRAS designation. In someembodiments, the active ingredients are non-prescription activeingredients, meaning an active ingredient having a pharmacologicaland/or physical effect on the body and which is not regulated by theUnited States Food and Drug Administration (USFDA) as a new drug.

The sustained-release beads of the dispersed phase may include a coatinglayer to further alter the rate of sustained-release of the activeingredients. Additional coating layers will generally result in a slowersustained-release of the active ingredients. In one embodiment, thecoating layer for the sustained-release beads is polymer-based coating.One type of polymer-based coating is a cellulose-based coating layer,such as an ethyl cellulose-based coating layer. In one embodiment, thecoating layer is a ^(SURELEASE)® coating layer as manufactured byColorcon of West Point, Pa. In some embodiments, the coating is aresin-based coating, such as a shellac-based coating. In someembodiments, the coating is a lipid-based coating, such as a fatty acidor wax-based coating. The coating may be added in any amount to thesustained-release beads. In one embodiment, the coating is added at lessthan about 15 wt % of the sustained-release bead. In some embodimentswhere a coating layer encapsulates an core of active ingredient to formthe sustained-release bead, the bead may include from 40 to 90 wt %active ingredient and from 10 to 40 wt % coating layer.

As with the dispersion medium, the sustained-release beads of thedispersed phase may include additional components to alter theconsistency, appearance, taste, smell, or shelf life of thesustained-release beads. These components may be added as eitheradditional ingredients in the sustained-release beads or as coatinglayers on the sustained-release beads. In one embodiment, a coloringagent is used to alter the color of the sustained-release beads. Thesustained-release beads may be colored by mixing dyes with the activeingredients and binding agents during the formation of thesustained-release beads. The sustained-release beads may also be coloredby coating the sustained-release beads with a liquid dye mixture (e.g.,OPADRY® coating as manufactured by Colorcon of West Point, Pa.). Coatingthe sustained-release beads with a liquid dye mixture may be followed byadding a transparent coating to the sustained-release beads. Thesustained-release beads may also be colored by using metallictranslucent colorings that may be applied during the manufacture of thesustained-release beads or as a coating to the sustained-release beads.

The size and shape of the sustained-release beads are also not limited.The shape of the sustained-release beads may include spheres, cubes, androds as well as any type of irregular shape. In one embodiment, the sizeof the sustained-release beads is such that the sustained-release beadsmay be seen in the suspension without need for magnification, but alsosuch that the sustained-release beads are not substantially felt in themouth or throat when being orally ingested. One suitable range for thediameter of the sustained-release beads is less than 5.0 mm, such asfrom 0.5 mm to 5.0 mm. The sustained-release beads may also be muchsmaller, such as on a micrometer or nanometer scale.

Once the sustained-release beads are orally ingested by a mammal, thesustained-release beads will generally travel to a location in thedigestive tract where conditions begin to break down thesustained-release beads. The conditions that break down the sustainedrelease beads can include any of the chemical components in the stomachor gastrointestinal tract, including acidic and basic conditions. Therate at which the conditions are able to break down thesustained-release is bead is controlled by the type and amount ofbinding agent used in the sustained-release beads, including anycoatings applied to the sustained-release beads. Sustained-release beadswith relatively minor amounts of binding agents will be broken downquickly in the digestive tract. Once broken down, the active ingredientsin the sustained-release beads become available to be taken up by thecirculatory system of the mammal. Sustained-release beads with higheramounts of binding agents and coatings will break down relativelyslowing, meaning that the active ingredients will not become availableto be taken up by the circulatory system until after a longer period oftime. In this manner, active ingredients may be provided to a mammalover a sustained period of time when sustained-release beads withvarying binding agent concentrations and coatings are included in thesuspension orally ingested by a mammal.

In another embodiment, a method for making sustained-release beads suchas the sustained-release beads described above and used in the dispersedphase of the suspension described above includes the extruding andunitizing of a mixture of binding agents and active ingredients. Asshown in FIG. 1, the method includes forming at 100 a blend of one ormore binding agents and one or more active ingredients, adding aqueoussolution to the to the blend at 110 to form a wet mass, extruding thewet mass at 120, and unitizing the extrudate at 130 to formsustained-release beads.

Blending together of the one or more active ingredients and the one ormore binding agents can be carried out according to any suitable methodfor blending two or more materials. In one embodiment, the one or moreactive ingredients and the one or more binding agents are in a powderform and are therefore blended by any known method for the blendingtogether of various powders. Blending can be carried out for anysuitable period of time and at any blending speed or rate. In oneembodiment, the blending is carried out for 3 minutes in a low shearplanetary mixer.

The initial amount of active ingredients and binding agents are notlimited and, in one embodiment, may generally be in accordance with theweight ranges described above in the description of thesustained-release beads of the dispersed phase. In this respect, thetotal amount of active ingredients may be from 5 wt % to 60 wt % of theblend and the total amount of the binding agent may be from 40 wt % to95 wt % of the blend. The total amount of active ingredients may includeone or more different active ingredients in any distribution and thetotal amount of binding agents may include one or more binding agents inany distribution. The active ingredients and binding agents suitable foruse in the manufacture of the sustained-release beads are identical tothe active ingredients and binding agents described in greater detail inthe previous embodiments.

Additional components as described in greater detail above can also beblended together with the binding agents and the active ingredients inorder to alter various characteristics of the beads resulting fromextruding and unitizing the blend.

Once the blend is formed, aqueous solution is added to the blend tocreate a wet mass. Aqueous solution can be added to the blend in anysuitable manner to create the wet mass. In one embodiment, the aqueoussolution and blend are mixed in order to ensure sufficient wetting ofthe blend and creation of an evenly wet mass of materials. The aqueoussolution is added to the blend at a solution to blend ratio of from0.1:1.0 to 1.0:1.0. In one embodiment, the ratio is 0.35:1.0.Preferably, the aqueous solution is water.

The wet mass is then passed through an extruder in order to form anextrudate. Any suitable extruder may be used to extrude the wet mass.Suitable extruders include screw extruders, screen extruders, gearextruders, cylinder extruders and radial extruders. The operatingconditions for the extruder are not limited and may be adjustedaccording to the user's requirements. The die for the extruder shouldgenerally be of a size approximate the desired cross sectional size forthe beads. Due to the pressure and heat that may be applied to the wetmass during extrusion, the extrusion process generally results in thehardening of the binding agent to create the structural framework forthe sustained-release bead and that maintains the active ingredientevenly dispersed throughout the sustained-release bead.

Extrudate is then unitized in order to form individual sustained-releasebeads. While having an appropriate cross-sectional size, the extrudateis typically of a length greater than desired for the individualsustained-release beads. Unitizing includes any process by which theextrudate is broken down into smaller units that fall within the desiredsize dimensions for the sustained-release beads. For example, if theextrudate is generally in the form of a long, cylindrical rod, the rodmay be cut along its length as part of the unitizing process to createsmaller rod-shaped sustained-release beads of the desired dimensions.Any unitizing method may be utilized in order to alter the extrudateinto the desired shape for the sustained-release beads. In oneembodiment where spherical sustained-release beads are desired, theextrudate may be sent to a spheronizer. Any suitable spheronizer and anysuitable operating conditions for the spheronizer may be used.

Once unitizing is completed, the sustained-release beads may undergofurther processing to refine the sustained-release beads. One suchprocess includes drying the sustained-release beads in order to remove asubstantial portion of the moisture still included in thesustained-release beads. In one embodiment, 85% or more of the moisturecontent of the sustained-release beads is removed by drying. Anysuitable method of drying may be used in order to remove the aqueoussolution content from the sustained-release beads. In another additionalprocessing step, the beads may be coated to further adjust thesustained-release of the sustained-release beads. In one embodiment, thecoatings are cellulose-based coatings, such as an ethyl cellulose-basedcoating. The addition of a coating will generally result in a slowersustained-release of the active ingredients than if thesustained-release bead does not include a coating. As discussed ingreater detail above, additional coatings may also be added in order tochange the color of the sustained-release beads.

In another embodiment, a beverage includes the suspension described ingreater detail above. The beverage provides the active ingredients ofthe sustained-release beads to a mammal that orally ingests thebeverage. The beverage generally includes a receptacle in which thesuspension is contained. A receptacle of any size, shape and materialthat is capable of containing the suspension may be used. In oneembodiment, the size of the receptacle is such that a single serving(e.g., 16.9 fl. oz.) can be contained in the receptacle. The receptaclemay also be configured so as to be easily gripped by one hand or fit ina beverage holder of an automobile. The receptacle may be made fromrecyclable or non-recyclable material. The receptacle may includelabeling or other indications of source and contents. The receptacle mayalso include a removable cap to secure the suspension in the receptaclewhen the suspension is not being ingested. The suspension contained inthe receptacle is identical to the suspension described in previousembodiments.

In another embodiment, packetized sustained-release beads are providedfor easy transport of sustained-release beads and addition ofsustained-release beads to any suitable fluid. The packetizedsustained-release beads generally include a packet and a selectedquantity of sustained-release beads contained in the packet.

The packet may be any suitable type of packet for containing thesustained-release beads. The packet may have any suitable size and shapeand may be made of any suitable material. In one embodiment, the packetis of a size suitable for containing a single serving ofsustained-release beads. The shape of the packet may be such that thedepth of the packet is small relative to the length and width of thepacket. In this manner, the packet has a generally flat shape andprovides enhanced portability. The material of the packet may be anysuitable material capable of containing the sustained-release beads.Such material may be recyclable or non-recyclable. In one embodiment,the material of the packet is paper, which allows for the packet to betorn open for access to the sustained-release beads contained therein.The packet may have other opening means, such as perforations, seals,adhesives, zippers, and ties.

The sustained-release beads contained in the packet are identical orsimilar to the beads described above in a previous embodiment. Theselected quantity of beads contained in the packet is not limited. Asnoted above, in one embodiment the selected quantity may be a singleserving of sustained-release beads. In this embodiment, the entirecontents of the packet may be emptied into a suitable receptaclecontaining a dispersion medium for creating a beverage as described in aprevious embodiment. The amount of sustained-release beads thatconstitute a single serving may vary depending on a variety of factors,including the mammal consuming the beads, the desired period ofsustained-release, and type and amount of active ingredients included inthe sustained-release beads.

In another embodiment, a method for producing an orally ingestible fluidis provided. As shown in FIG. 2, the method includes providing one ormore sustained-release beads at 200, providing a dispersion medium at210, and mixing the one or more sustained-release beads in thedispersion medium at 220. The resulting orally ingestible fluid may beingested by a mammal to thereby provide the sustained-release beads inthe digestive tract of the mammal. In the digestive tract, thesustained-release beads begin to break down due to the presence ofvarious chemical components in the digestive tract. The rate at whichthe digestive tract breaks down the sustained-release beads iscontrolled by the amount of binding agent included in thesustained-release beads. Higher amounts of binding agents in thesustained-release beads, including coatings, will generally result in aslower break down of the beads. Once the beads are sufficiently brokendown, the active ingredients become available to be taken up by thecirculatory system of the mammal.

The one or more sustained-release beads provided in one step of themethod are identical or similar to the sustained-release beads describedin the previous embodiments. The dispersion medium provided in anotherstep of the method is identical or similar to the dispersion mediumdescribed in previous embodiments.

The dispersion medium and the sustained-release beads are then mixedtogether in order to produce the orally ingestible fluid. Any manner ofmixing the dispersion medium and the sustained-release beads togethermay be used, including pouring the sustained-release beads into thedispersion medium or vice versa. Additionally, any ratio of dispersionmedium and sustained-release beads may be used. In one embodiment, themixing of the dispersion medium and the sustained-release beads isconducted such that the sustained-release beads are suspended in thedispersion medium and evenly distributed throughout the dispersionmedium.

The orally ingestible fluid may be customizable based on a specificorder placed by a customer. More specifically, various sustained-releasebeads having various active ingredients may be provided and mixed withthe dispersion medium to provide a fluid that specifically addresses theneeds of a customer. For example, where a customer desires an orallyingestible fluid capable of providing stimulation and energy, thesustained-release beads mixed with the dispersion medium may have arelatively large amount of caffeine or other stimulants.

In one embodiment, specialized orally ingestible fluids may be preparedby an automated assembly line. Receptacles for containing the orallyingestible fluid may be moved along a suitable transportation device,such as a conveyor belt, and under various dispensers containingsustained-release beads with varying compositions. As the receptaclemoves along the conveyor belt and under the various dispensers, thedispensers may dispense or not dispense sustained-release beads into thereceptacles based on the order of the customer and a computer programproviding information to the dispensers regarding when to dispensesustained-release beads and when not to dispense sustained-releasebeads. The dispensers can also operate in accordance with computerprogramming instructions to vary how much of each type ofsustained-release bead to dispense into the receptacle. The receptaclespassing under the dispensers may already contain the dispersion medium,or the dispersion medium may be added after the sustained-release beadshave been dispenses in the receptacles. The assembly line may alsoinclude mechanisms for shaking the receptacles after both dispersionmedium and the specifically ordered sustained-release beads have beendispensed therein in order to evenly distribute the sustained-releasebeads throughout the dispersion medium.

An ordering system is also contemplated, wherein a customer may remotelyplace orders for specialized orally ingestible fluids or components ofthe orally ingestible fluids. In one embodiment, the ordering systemincludes the ability to order various sustained-release beads to suitthe specific needs of the customer. For example, customers desiringsustained-release beads including active ingredients that can assist aconsumer during periods of exercise may order sustained-release beadsincluding electrolytes and stimulants. Customer may also include medicalprofessionals who place orders for sustained-release beads that meet thehealth needs of their patients. Such system may include the ability toorder over the telephone, via the Internet or through the mail.

In embodiments where sustained-release beads are ordered by a customer,the ordering method may further include receipt of the sustained-releasebeads ordered by the customer, and mixing the sustained-release beadswith an appropriate dispersion medium to create an orally ingestiblefluid. The appropriate dispersion medium may be obtained by the customerseparately from the sustained-release beads. The beads may be mixed withthe dispersion medium in any suitable manner, and in one embodiment, thebeads are added to the dispersion medium followed by shaking thedispersion medium to disperse the beads throughout the dispersionmedium.

Sustained-release beads received by a customer may also be dispensed inother non-solid food products. For example, sustained-release beads maybe poured into a yogurt, shake or meal replacement beverage and stirredamongst the food. Consequently, consumption of the food product willprovide the active ingredients of the sustained-release beads to theindividual consuming the food product.

In another embodiment, a sports drink includes sustained-release beadshaving one or more active ingredients that tend to be depleted in amammal during or after periods of exercise or that aid a mammal whenpreparing for, engaging in, or recovering from exercise. Accordingly,the sports drink may be orally ingested by a mammal before, during orafter periods of exercise in order to provide the one or more activeingredients to the mammal undertaking the exercise.

The sports drink generally includes a fluid receptacle and a suspension.The fluid receptacle contains the suspension and generally includes abase, a surrounding sidewall extending upwardly from the base toterminate in an open mouth, and a closure adapted to releasably coverthe open mouth. The suspension is identical to the suspension describedin greater detail above, and generally includes a dispersion medium anda dispersed phase of one or more sustained-release beads.

The fluid receptacle of the sports drink is illustrated in FIG. 3. Thefluid receptacle 300 includes a base 310, a surrounding sidewall 320extending upwardly from the base 310 to terminate in an open mouth 330,and a closure 340 adapted to releasably cover the open mouth 330.

As shown in FIG. 3, the fluid receptacle 300 has a generally cylindricalshape, including a circular base 310 and a surrounding sidewall 320 thatis generally perpendicular to the circular base 310. However, the fluidreceptacle 300 may have any suitable shape. The base 310 may be anyshape and the surrounding sidewall 320 may be non-perpendicular to thebase 310. The surrounding sidewall 320 may also be curved and contoured,rather than straight and flat as shown in FIG. 3. To this end, both thefluid receptacle 300 and the closure 340 can assume any of a variety ofknown or hereinafter developed configurations for accommodating thecontents thereof. As also shown in FIG. 3, the sidewall 320 tapers atthe end opposite the base 310 to terminate at an open mouth 330. Thesidewall 320 need not taper as shown in FIG. 3, and may also flareoutwardly. The size and shape of the open mouth 330 are not limited. Theopen mouth 330 generally provides access to the interior of the fluidreceptacle 300 as bound by the base 310 and sidewall 320.

FIG. 3 further illustrates a closure 340. The closure 340 can be adaptedto releasably cover the open mouth 330. The size and shape of theclosure 340 are not limited. In one embodiment, the closure 340 has asimilar shape and size as the open mouth 330. The closure 340 mayreleasably engage the open mouth 330 in any suitable manner. In oneembodiment, the closure 340 engages the open mouth 330 in a fluid-tightseal so as to prevent fluid contained within the receptacle 300 fromescaping the receptacle 300 via the open mouth 330. Exemplary mannersfor the closure 340 to releasably engage the open mouth 330 include, butare not limited to, an interference fit between the open mouth 330 andthe closure 340 and a male and female thread system for screwing andunscrewing the closure 340 on and off the open mouth 330. In The closure340 may also take the form of a material that covers the open mouth 330and may be punctured to access the interior of the receptacle 300.

The overall size of the receptacle 300 is not limited. The size ofreceptacle may be suitable for containing a single serving of thesuspension or may be large enough to include multiple servings of thesuspension.

The materials of the receptacle 300 are not limited. In one embodiment,the materials of the receptacle 300 are fluid-impermeable so as tocontain the suspension therein without leaks. The materials may berecyclable or non-recyclable. The receptacle 300 may also includeindicia of source or contents, such as labels affixed to the exterior ofthe sidewall 320.

The suspension contained in the receptacle 300 is identical or similarto the suspension described in greater detail above, but specificallyincludes sustained-release beads having active ingredients of the typethat tend to be depleted by a mammal during or after exercise or thataid a mammal when preparing for, engaging in, or recovering fromexercise. Exemplary active ingredients for the sustained-release beadsinclude electrolytes, such as potassium, magnesium, sodium, and calcium,stimulants, such as caffeine, and vitamins and minerals, such asvitamins B1, B2, B3, B5, B6 and B12.

Any suitable amount of the binding agents and active ingredients can beused for the sustained-release beads. In one embodiment, the totalamount of the binding agents in the sustained-release beads is from 40wt % to 95 wt % of the sustained-release beads and the total amount ofthe active ingredients in the sustained-release beads is from 5 wt % to60 wt % of the sustained-release beads. In one embodiment, thesuspension includes a variety of sustained-release beads havingdifferent compositions. The composition of the sustained-release beadsmay vary in both the type and amount of active ingredients and the typeand amount of the binding agents. In this manner, the sports drink mayprovide various types and amounts of active ingredients to the mammal atvarious times. For example, the sports drink may include a first set ofsustained-release beads including caffeine with relatively small amountsof binding agent and a second set of sustained-release beads includingelectrolytes with relatively large amounts of binding agent. Wheningesting the sports drink having these types of sustained-releasebeads, the mammal will be provided with caffeine shortly after ingestionof the sports drink to help provide energy at the start of the period ofexercise and then will be provided with electrolytes after a period oftime during which electrolytes in the mammals body may have beendepleted by the exercise. In another example, the sports drink includesvarious sustained-release beads all having electrolytes, but withvarying amounts of binding agent. In this example, the ingested sportsdrink will provide electrolytes to the mammal over an extended period oftime that may coincide with the period of exercise. In this manner, thesustained-release beads provide electrolytes to the mammal over theentire course of the exercise to replenish electrolytes lost during theperiod of exercise without requiring the mammal to ingest the sportsdrink at several instances over the course of the period of exercise.

EXAMPLES Example 1 Sustained-Release Bead Preparation Method

The following mixture of powders was mixed for 3 minutes in a low shearplanetary mixer.

500 g Caffeine

300 g Potassium Chloride

150 g Sodium Chloride

950 g Microcrystalline cellulose

100 g Methocel E5

700 kg of water was then added to the powder mixture to produce a wetmass. The wet mass was passed through an LCI extruder at 50 rpm. Theextrudate was spheronized in an LCI spheronizer at 1000 rpm for 1 minuteto produce spherical beads. The spherical beads had a moisture contentof 38.36 wt %. The spherical beads were dried in a Glatt GPCG-3 untilthe moisture content was reduced to 4.32 wt %. Optionally, the sphericalbeads were coated with SUBLEASE to a 10% theoretical weight gain and/orOPADRY II to a 4% theoretical weight gain.

Example 2 Dispersion Medium Preparation Method (Agar-Agar)

2.2 grams of Agar-Agar were combined with 1000 mL of water in a Pyrexglass container. The solution of Agar-Agar and water was then brought toa boil utilizing a heat/stir plate. Boiling continued at 75% heat for 15minutes or until the Agar-Agar particles completely dissolved in thesolution. The water level of the solution was then reconstituted to 1000mL. The solution was allowed to cool, followed by the combining 500 mLof the solution with 100 mL of drink syrup concentrate and 100 mL offructose syrup. The combination of solution, drink syrup concentrate andfructose syrup was mixed well. Sustained release beads prepared by themethod described in Example 1 were then added to the mixture to yield afinal bead concentration of 500 mg/500 mL.

Example 3 Dispersion Medium Preparation Method (Xanthan Gum)

2.4 grams of Xanthan gum were added to the 1000 mL of water. The Xanthangum and water were mixed in an industrial strength blender on low speedfor 60 seconds. The blended solution was transferred to a Pyrex glasscontainer and mixed well with a stir plate. 500 mL of the solution wasthen combined with 100 mL of drink syrup concentrate and 100 mL offructose syrup and mixed well. Sustained release beads prepared by themethod described in Example 1 were then added to the mixture to yield afinal bead concentration of 500 mg/500 mL.

Example 4 Dispersion Medium Preparation Method (Agar-Agar and XanthanGum)

1.5 grams of Agar-Agar were combined with 1000 mL of water in a Pyrexglass container. The solution of Agar-Agar and water was then brought toa boil utilizing a heat/stir plate. Boiling continued at 75% heat for 15minutes or until the Agar-Agar particles completely dissolved in thesolution. The water level of the solution was then reconstituted to 1000mL. The solution was allowed to cool, followed by the addition of 1.1grams of Xanthan gum to the Agar-Agar and water solution. The combinedAgar-Agar/Xanthan gum solution was then mixed in an industrial strengthblender on low speed for 60 seconds. The blended solution was thentransferred to a Pyrex glass container and mixed with using a stirplate. 500 mL of the blended solution was then combined with 100 mLdrink syrup concentrate and 100 mL of fructose syrup. The combination ofingredients was mixed well. Sustained release beads prepared by themethod described in Example 1 were then added to the mixture to yield afinal bead concentration of 500 mg/500 mL.

As used herein, spatial or directional terms, such as “left,” “right,”“front,” “back,” and the like, relate to the subject matter as it isshown in the drawing Figures. However, it is to be understood that thesubject matter described herein may assume various alternativeorientations and, accordingly, such terms are not to be considered aslimiting. Furthermore, as used herein (i.e., in the claims and thespecification), articles such as “the,” “a,” and “an” can connote thesingular or plural. Also, as used herein, the word “or” when usedwithout a preceding “either” (or other similar language indicating that“or” is unequivocally meant to be exclusive—e.g., only one of x or y,etc.) shall be interpreted to be inclusive (e.g., “x or y” means one orboth x or y). Likewise, as used herein, the term “and/or” shall also beinterpreted to be inclusive (e.g., “x and/or y” means one or both x ory). In situations where “and/or” or “or” are used as a conjunction for agroup of three or more items, the group should be interpreted to includeone item alone, all of the items together, or any combination or numberof the items. Moreover, terms used in the specification and claims suchas have, having, include, and including should be construed to besynonymous with the terms comprise and comprising.

Unless otherwise indicated, all numbers or expressions, such as thoseexpressing dimensions, physical characteristics, etc., used in thespecification (other than the claims) are understood as modified in allinstances by the term “approximately.” At the very least, and not as anattempt to limit the application of the doctrine of equivalents to theclaims, each numerical parameter recited in the specification or claimswhich is modified by the term “approximately” should at least beconstrued in light of the number of recited significant digits and byapplying ordinary rounding techniques.

In addition, all ranges disclosed herein are to be understood toencompass and provide support for claims that recite any and allsubranges or any and all individual values subsumed therein. Forexample, a stated range of 1 to 10 should be considered to include andprovide support for claims that recite any and all subranges orindividual values that are between and/or inclusive of the minimum valueof 1 and the maximum value of 10; that is, all subranges beginning witha minimum value of 1 or more and ending with a maximum value of 10 orless (e.g., 5.5 to 10, 2.34 to 3.56, and so forth) or any values from 1to 10 (e.g., 3, 5.8, 9.9994, and so forth).

I/we claim:
 1. A sustained-release bead consisting of: a core includingone or more active ingredients and optionally water; and at least onecoating layer encapsulating the core.
 2. The sustained-release bead ofclaim 1, wherein the core includes water.
 3. The sustained-release beadof claim 1, wherein the one or more active ingredients arenon-prescription active ingredients.
 4. The sustained-release bead ofclaim 1, wherein the one or more active ingredients are GRAS-designatedactive ingredients.
 5. The sustained-release bead of claim 1, whereinthe one or more active ingredients are selected from the groupconsisting of stimulants, electrolytes, vitamins, minerals, orcombinations thereof.
 6. The sustained-release bead of claim 1, whereinthe one or more active ingredients are selected from the groupconsisting of proteins, amino acids, hormones, organic acids, orcombinations thereof.
 7. The sustained-release bead of claim 1, whereinthe coating layer includes a polymer coating or a resin coating.
 8. Thesustained-release bead of claim 1, wherein the sustained release beadcomprises from 40 to 90 wt % of the one or more active ingredients andfrom 10 to 40 wt % of the at least one coating layer.
 9. Asustained-release bead consisting essentially of: a core including oneor more active ingredients and optionally water; and at least onecoating layers encapsulating the core.
 10. The sustained-release bead ofclaim 9, wherein the core includes water.
 11. The sustained-release beadof claim 9, wherein the one or more active ingredients arenon-prescription active ingredients.
 12. The sustained-release bead ofclaim 9, wherein the one or more active ingredients are GRAS-designatedactive ingredients.
 13. The sustained-release bead of claim 9, whereinthe one or more active ingredients are selected from the groupconsisting of stimulants, electrolytes, vitamins, minerals, orcombinations thereof.
 14. The sustained-release bead of claim 9, whereinthe one or more active ingredients are selected from the groupconsisting of proteins, amino acids, hormones, organic acids, orcombinations thereof.
 15. The sustained-release bead of claim 9, whereinthe coating layer includes a polymer coating or a resin coating.
 16. Thesustained-release bead of claim 9, wherein the sustained release beadcomprises from 40 to 90 wt % of the one or more active ingredients andfrom 10 wt % to 60 wt % of the at least one coating layer.